Modulation of NRF2 and CYP24A1 Pathways by Hookah Smoke: Implications for Male Reproductive Health

Antioxidants act by preventing excessive oxidative stress within the developing sperm cells. Hookah smoking has been implicated in inducing oxidative stress which may be a risk factor for male infertility. This study aims to bridge this knowledge gap by evaluating the effect of hookah smoking on sperm quality and the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) genes which are involved in antioxidant response. Young fertile men in reproductive age were categorized into hookah smokers (n = 32) and non-smokers (n=52). Sperm parameters (concentration, volume, motility, morphology) as well as gene expression of NRF2 and CYP24A1 were evaluated in each sperm sample. There was no meaningful change in sperm parameters in the case group compared with the controls. The mRNA levels of NRF2 was significantly higher in the case group compared with the controls (p = 0.01), while CYP24A1 expression did not significantly change between the study groups. A remarkable increase in NRF2 expression in hookah smokers might be a cellular defense mechanism, indicating activation of antioxidant response in sperm to counteract potential oxidative stress caused by hookah use. However, further research is needed to understand the functional consequences of this upregulation.